CYP2D6 GENETIC POLYMORPHISM AND EXTRAPYRAMIDAL SIDE EFFECTS OF ANTIPSYCHOTIC DRUGS
Keywords:
schizophrenia, antipsychotics, extrapyramidal side effects, genetic polymorphism, CYP2D6, genotype, phenotype, pharmacogeneticsAbstract
Background. Antipsychotics and also some other psychiatric and some non-psychiatric drugs are known to cause extrapyramidal symptoms. Some of these symptoms, e.g. tardive dyskinesia, may be irreversible and may have an important influence on the quality of life. Various factors are involved in the etiopatogenesis of extrapyramidal symptoms. Genetic polymorphism of the CYP2D6 izoenzyme and its eventual association with the emergence of extrapyramidal symptoms are described by the authors, since the majority of antipsychotic drugs are metabolised through the CYP2D6 metabolic pathway. Various CYP2D6 phenotyping and genotyping methods and possible associations between genotype and phenotype are described, and in an overview of several clinical studies the results of some of them corroborate the role of genetic polymorphism in the emergence of extrapyramidal side effects of antipsychotic drugs, while in the others no association was observed.
Conclusions. CYP2D6 genotype or phenotype may not yet have a precise role in the extrapyramidal side effects of antipsychotic drugs, although it may indubitably be used to distinguish the patients with therapeutic problems caused by the changes in the metabolism of drugs that are substrates for CYP2D6 from these patients, who may have therapeutic problems caused by other mechanism of antipsychotic drugs’ activity. In this way the pharmacogenetics exerts an evermore important influence on a daily use of various drugs.
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